(Z)-Endoxifen for the Treatment of Premenopausal Women With ER+/HER2- Breast Cancer

Overview

About this study

The purpose of this study is to identify a (Z)-endoxifen dose that achieves (Z)-endoxifen steady-state plasma concentrations (Css) between 500-1000 ng/mL. Dosing will begin with the (Z)-endoxifen 40 mg/day dose and may additionally explore either a lower (20 mg/day) or higher (80 mg/day) dose level based on (Z)-endoxifen Css as well as toxicity.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

Each patient must meet the following criteria to be enrolled in PK Run-in Cohort or the Treatment Cohort of this study:

  • Female sex assigned at birth.
  • ≥ 18 years of age.
  • Not lactating, pregnant, or planning to become pregnant in the next year and agrees to take adequate steps to prevent becoming pregnant 7 days before beginning treatment, during treatment and for 9 months after last dose and not breast feeding during treatment and for 3 months after last dose.
  • Must agree to one non-hormonal highly effective method of contraception for the entire duration of study participation. Highly effective methods of birth control are defined as those, alone or in combination, that resulted in a low failure rate of < 1% per year when used consistently and correctly such as intrauterine devices (IUDs, non-hormonal such as copper IUD), sexual abstinence or vasectomized partner. Barrier contraceptives (e.g., male condom or diaphragm) are acceptable if used in combination with spermicides (e.g., foam, gel).
  • Premenopausal defined as any female who has experienced menarche and does not meet any of the following criteria for postmenopausal:
    • Permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral oophorectomy, or bilateral salpingectomy); or
    • Amenorrheic for 12 or more months; or
    • Amenorrheic for < 12 or more months and follicle-stimulating hormone (FSH) or plasma estradiol are in the postmenopausal range.
  • Pathologic confirmation of strongly estrogen receptor positive (ER+) (defined as estrogen receptor [ER] ≥ 67% or Allred Score 6-8) by local institution protocol.
  • Eastern Cooperative Oncology Group ECOG Performance Status (ECOG PS) of 0 to 2.
  • Nottingham Grade 1 or 2.
  • HER2- breast cancer (histologically confirmed) using American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines defined as one of the following:
    • 0 or 1+ by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) not done;
    • 0 or 1+ by IHC and not amplified by FISH;
    • 2+ by immunohistochemistry with average of < 4.0 HER2 signals per cell and an HER2/CEP17 ratio ≥ 2.0;
    • 2+ by immunohistochemistry with average of ≥ 4.0 and < 6.0 HER2 signals per cell and an HER2/CEP17 ratio < 2.0;
    • IHC not done and not amplified by fluorescence in situ hybridization (FISH).
  • Clinical Stage IIA or IIB invasive breast cancer (per American Joint Committee on Cancer [AJCC] 8th edition clinical staging) see Appendix 10.
  • Largest tumor diameter2.0 cm either by imaging or clinical examination.
  • Magnetic resonance imaging (MRI) ≤ 30 days of registration.
  • Mammogram performed ≤ 90 days of registration (Treatment Cohort only).
  • Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
  • Willing to provide tissue samples for research purposes.

Exclusion Criteria: 

Subjects who meet any of the following criteria will be excluded from the PK Run-in Cohort and the Treatment Cohort:

  • Inflammatory breast cancer defined as clinically significant erythema of the breast and/or documented dermal lymphatic invasion.
  • Any prior diagnosis or treatment for breast cancer, including carcinoma in situ, or history of any other active malignancy within the past 2 years prior to study entry, with the exception of:
    • Adequately treated in situ carcinoma of the cervix uteri;
    • Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin;
    • Any other malignancy with a life expectancy of more than 2 years.
  • Any uncontrolled intercurrent illness including, but not limited to:
    • Ongoing or active infection requiring systemic treatment with strong inhibitors/inducers of CYP450 enzymes (including bacterial infection, fungal infection, or detectable viral infection).;
    • Symptomatic congestive heart failure;
    • Unstable angina pectoris;
    • Uncontrolled symptomatic cardiac arrhythmias;
    • Uncontrolled hypertension (defined as blood pressure > 160/90 mm Hg);
    • Uncontrolled diabetes (Hemoglobin A1c [HbA1c] > 50 mmol/mol);
    • Marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval > 470 milliseconds [msec]) using Fridericia’s QT correction formula seen ≤ 28 days of registration.
  • Any of the following co-morbid conditions:
    • Known cataracts or retinopathy;
    • History of deep vein thrombosis (DVT)/pulmonary embolism (PE);
    • Known activated protein C (APC) resistance, an inherited coagulation disorder.
  • Evidence of the following laboratory abnormalities ≤ 28 days prior to registration:
    • Creatine clearance < 60 ml/hr by the Cockcroft-Gault equation;
    • Total bilirubin ≥ 1.5 x upper limit of normal (ULN);
    • Aspartate aminotransferase (AST) or alanine amino transferase (ALT) ≥ 2.5 x ULN;
    • Platelet count (PLT) ≤ 75,000/mm^3 ;
    • Hemoglobin (Hb) ≤ 10 g/dL.
  • Hormonal therapies including birth control and hormone replacement therapy during the study or within 1 week of registration.
  • Allergy to endoxifen, goserelin, or exemestane or any of their components.
  • Participation in another investigational clinical trial ≤ 6 months of registration.
  • Not willing or able to understand the study information and/or informed consent.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 11/7/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Matthew Goetz, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Pooja Advani, M.B.B.S., M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Lida Mina, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available
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CLS-20542688

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